Myelofibrosis (MF) is a bone marrow illness that affects blood-forming tissues in the body. MF disturbs the body's normal production of blood cells, causing extensive scarring in the bone marrow. This leads to severe anemia, weakness, fatigue, and an enlarged spleen. The purpose of this study is to see how safe and tolerable ABBV-744 is, when given alone, and in combination with ruxolitinib or navitoclax, for adult participants with MF. ABBV-744 is an investigational drug being developed for the treatment of MF. The study has 4 segments - A, B, C, and D. In Segment A, the safe dosing regimen of ABBV-744 is identified and then, given alone as monotherapy. In Segment B, C, and D, combination therapies of ABBV-744 with either ruxolitinib or navitoclax are given. Adult participants with a diagnosis of MF will be enrolled. Around 130 participants will be enrolled in 60 sites worldwide. In Segment A, participants will receive different doses and schedules of oral ABBV-744 tablet to identify safe dosing regimen. Additional participants will be enrolled at the identified monotherapy dosign regimen. In Segment B, participants will receive oral ruxolitinib and ABBV-744 will be given as "add-on" therapy. In Segment C, participants will receive ABBV-744 and oral navitoclax. In Segment D, participants will receive ABBV-744 and ruxolitinib. Participants will receive treatment until disease progression or the participants are not able to tolerate the study drugs. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of treatment will be checked by medical assessments, blood and bone marrow tests, checking for side effects, and completing questionnaires.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
21
University of California, Davis Comprehensive Cancer Center /ID# 221790
Sacramento, California, United States
Duplicate_Dartmouth-Hitchcock Medical Center - 1 Medical Center Drive /ID# 224623
Lebanon, New Hampshire, United States
Roswell Park Cancer Institute /ID# 222557
Buffalo, New York, United States
The Mount Sinai Hospital /ID# 221549
New York, New York, United States
Weill Cornell Medical College /ID# 227069
New York, New York, United States
Percentage of Participants With Adverse Events
An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with the treatment. The investigator assesses the relationship of each event to the use of study drug.
Time frame: Up to Approximately 1 year from start of study
Percentage Of Participants Who Achieve Spleen Volume Reduction Of 35% Or Greater (SVR35)
Reduction in spleen volume is measured by magnetic resonance imaging (MRI) or computed tomography (CT) scan.
Time frame: Up To Week 24
Maximum Observed Plasma Concentration (Cmax) of ABBV-744
Maximum observed plasma concentration (Cmax) of ABBV-744.
Time frame: Up To Week 12
Time To Cmax (Tmax) Of ABBV-744
The amount of time taken to reach Cmax.
Time frame: Up To Week 12
Area Under The Concentration Versus Time Curve (AUC) Of ABBV-744
AUC of ABBV-744 will be calculated.
Time frame: Up To Week 12
Half-Life (t1/2) Of ABBV-744
Half-life of ABBV-744 will be calculated.
Time frame: Up To Week 12
Accumulation Ratio Of ABBV-744
Pharmacokinetic parameters will include accumulation ratio of ABBV-744.
Time frame: Up To Week 12
Apparent Clearance (CL/F) Of ABBV-744
CL/F of ABBV-744 will be calculated.
Time frame: Up To Week 12
Apparent Volume Of Distribution (Vd/F) Of ABBV-744
Vd/F of ABBV-744 will be calculated.
Time frame: Up To Week 12
Percentage Of Participants With >= 50% Reduction In Total Symptom Score (TSS)
TSS is assessed using the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0. MFSAF v4.0 measures the burden of myelofibrosis-related symptoms. The symptoms are assessed on a 11-point numeric rating scale (NRS) anchored from 0 (absent) to 10 (worst imaginable).
Time frame: Up to Week 24
Objective Response Rate (ORR)
ORR is defined as the sum of rates of partial remission (PR) or better.
Time frame: Week 24
Maximum Observed Plasma Concentration (Cmax) Of Navitoclax
Maximum Observed Plasma Concentration (Cmax) Of Navitoclax.
Time frame: Up To Week 12
Time To Cmax (Tmax) Of Navitoclax
The amount of time taken to reach Cmax.
Time frame: Up To Week 12
Area Under The Concentration Versus Time Curve (AUC) Of Navitoclax
AUC of Navitoclax will be calculated.
Time frame: Up To Week 12
Maximum Observed Plasma Concentration (Cmax) Of Ruxolitinib
Maximum Observed Plasma Concentration (Cmax) Of Ruxolitinib.
Time frame: Up To Week 12
Time To Cmax (Tmax) Of Ruxolitinib
The amount of time taken to reach Cmax.
Time frame: Up To Week 12
Area Under The Concentration Versus Time Curve (AUC) Of Ruxolitinib
AUC of Ruxolitinib will be calculated.
Time frame: Up To Week 12
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Gabrail Cancer Center Research /ID# 222802
Canton, Ohio, United States
University of Oklahoma, Stephenson Cancer Center /ID# 224095
Oklahoma City, Oklahoma, United States
Oregon Health and Science University /ID# 221801
Portland, Oregon, United States
Texas Oncology- Baylor Charles A. Sammons Cancer Center /ID# 240004
Dallas, Texas, United States
VA Puget Sound Health Care System /ID# 224208
Seattle, Washington, United States
...and 33 more locations